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Kidney Week

Abstract: FR-PO1036

Efficiency and Safety of mTOR Inhibitors for Tuberous Sclerosis Complex-Associated Renal Angiomyolipoma

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Andronesi, Andreea, Fundeni Clinical Institute, Bucharest, Romania
  • Obrisca, Bogdan, Fundeni Clinical Institute, Bucharest, Romania
  • Sorohan, Bogdan Marian, Fundeni Clinical Institute, Bucharest, Romania
  • Andronesi, Danut, Fundeni Clinical Institute, Bucharest, Romania
  • Cristache, Cristina, Fundeni Clinical Institute, Bucharest, Romania
  • Ismail, Gener, Fundeni Clinical Institute, Bucharest, Romania
Background

Kidney involvement is the most important cause of morbidity and mortality in adult patients with tuberous sclerosis complex (TSC). mTOR inhibitor Everolimus (EVE) is the only pathogenic treatment approved. Since TSC is a rare genetic disease, long-term experience with EVE is still limited.

Methods

TSC patients treated with EVE for renal angiomyolipoma (AML) at increased bleeding risk without immediate surgery indication were followed prospectively. Kidney CT or MRI (same modality throughout the study for each patient) was done at baseline and annually thereafter. Treatment response was evaluated as percentage of reduction of sum of volumes of all target AML identified at baseline. Adverse events (AE) were graded according to the CTCAE v3.0.

Results

Between January 2015-May 2018 17 patients (12F, 5M), mean age 34.8+7.5 years (17-61), started treatment with EVE. Baseline diameter of the biggest AML was 7.7+2.8 cm (3.8-12), 7 patients had a history of spontaneous AML bleeding with 4 of them suffering total one-sided nephrectomy. Baseline eGFR was 78.8+36.1 ml/min/1.73 m2 CKD-EPI (9-126): 5 patients had stage 2 CKD, 1 patient stage 3, 2 patients stage 4 and 1 patient stage 5. Initial EVE dose was 10 mg/day, with dose adjustments according to target trough level (5-15 mcg/l) and tolerance. Total treatment period was 23.4+11.4 months (5-45). 69.2% of patients had a more than 30% response after 12 months and the proportion of patients with response ≥50% increased over time. No patient had new bleeding episodes, neither increase in AML volume or new AML (Table 1). All patients experienced AE, the most frequent one being dyslipidemia in 16 patients. The severity of AE was grade 1 or 2, with maximum incidence during the first 12 months, with no need for permanent treatment withdrawal.

Conclusion

Treatment of TSC-associated renal AML with EVE is efficient and well tolerated. mTOR pathway regulates many major cellular processes, so AE to EVE are frequent. Since this is a life-time treatment, careful surveillance is essential to rapidly identify and treat these AE.